I. Cholinesterase-Inhibiting Phosphoric Ester Poisoning
Among other uses, cholinesterase-inhibiting phosphoric esters are used as insecticides in agriculture. Cholinesterase-inhibiting phosphoric esters also have a toxic effect on human beings. Agricultural workers therefore are subject to periodic acute exposure through inhalation, oral ingestion or percutaneous absorption. As compared to insecticides, the compounds tabun, sarin, soman and VX, nerve warfare agents, are distinguished by a particularly high toxicity. All of these compounds are more or less strong inhibitors of acetylcholinesterase, an enzyme which physiologically blocks the effect of the transmitter acetylcholine released at certain nerve endings. Most poisoning symptoms caused by cholinesterase inhibitors are produced by an inundation with endogenic acetylcholine in the absence of acetylcholinesterase activity.
Currently, the basic drug therapy for such poisonings involves administering parasympatholytic atropine, blocking the exceeding muscarinic acetylcholine effects (e.g., increase of secretion in the respiratory system, bronchospasm, inhibition of the central nervous respiratory drive). There is no suitable antagonist available to normalize the exceeding nicotinic acetylcholine actions (e.g., inhibition of the impulse transmission at the synapses of motorial nerves to the respiratory musculature and to other skeletal muscles up to a complete peripheral motor paralysis). The peripherally caused myoparesis can only be compensated by oximes, e.g., pralidoxime (PAM) or obidoxime (Toxogonin™) which reactivate the inhibited acetylcholinesterase.
Some of the phosphoric cholinesterase inhibitors cleave alkyl residues after accumulation to the acetylcholinesterase, thus stabilizing the bond (“aging”). The aged esterase inhibitor complex cannot be reactivated by oximes. For poisoning by the nerve warfare agent soman, aging occurs after only 2 to 5 minutes. Therapy with atropine and oximes is absolutely insufficient for soman poisoning. The effectiveness of atropine and oximes can be considerably improved by preliminary treatment with indirect parasympathomimetics, e.g., carbamic acid esters, such as pyridostigmine and physostigmine. Carbamic acid esters inhibit the acetylcholinesterase in a manner similar to that of phosphoric esters. However, the bond between the two has a shorter duration and is completely reversible. Because the carbamates inhibit part of the acetylcholinesterase, if dosed suitably, carbamate-inhibited acetylcholinesterases are not available for interaction with phosphoric esters and phosphonates, which have a stronger and prolonged inhibition. This may well be a decisive factor for the protective action of carbamic acid esters, provided that the pretreatment started in time.
Preferably, preventing phosphorylation of the acetylcholinesterase reduces the risk of life threatening effects of exposure to these agents. Physical barriers, including respirators, protective suits, creams or ointments may reduce the likelihood of exposure. Nevertheless, treating a poisoning caused by organophosphorus insecticides requires prompt medical care. Since medical care for harvesters cannot always be accomplished promptly, there is a need for drugs to prophylactically counteract an intoxication. The use of carbamic acid esters for this purpose has already been described (Leadbeater, L. Chem. in Brit. 24, 683, 1988). The same applies to the effectiveness of carbamic acid esters in the pretreatment of a soman poisoning in animal experiments (Fleischer, J. H., Harris, L. W. Biochem. Pharmacol. 14, 641, 1965, Berry, W. K., Davies, D. R. Biochem. Pharmacol, 19, 927, 1970). Effective prophylactic drug dosages must not impair reactivity and functional capacity. However, carbamic acid esters have a low therapeutic index. As compared to pyridostigmine, an increased protective action can be achieved by physostigmine, but the side effects are more severe.
Other approaches include a prophylactic antidote consisting of a combination of pyridostigmine or physostigmine and N-methyl-4-piperidyl-1-phenylcyclopentane carboxylate-hydrochloride or arpenal, sycotrol, carmiphene or benactyzine, and, as an additional compelling component, a tranquilizer, i.e., diazepam or clonazepam. The undesired effects of physostigmine or pyridostigmine cannot be suppressed by the listed parasympatholytics alone. This requires additional administration of tranquilizers, which have problematic side effects.
II. Chlorophyll and Derivatives Thereof
Chlorophyll, and derivatives thereof, have therapeutic value, but typically only as diet ingested materials, or as substantially impure materials. The chemical structures for these compounds are provided below.

Evaluating therapeutic results using dietary ingestion, or administration of impure materials, has hindered efforts to assess the effectiveness of such compounds and pharmaceutical compositions comprising such compounds. One reason for this is that chlorophyll is a highly reactive molecule that must be handled with care during isolation procedures. It is susceptible to degradation by light, heat, oxidizing agents, acids and bases. Reactions that typify the sensitivity of chlorophyll include allomerization (oxidation), epimerization, particular at C-13, demetallation, de-phytylation, trans-esterification and decarboxymethylation at C-13. The reactivity of chlorophyll has limited preparatory methods to producing only small quantities of material, and such material typically is not as pure as would be desired.
Nevertheless, some isolation/production technologies have been reported, as indicated by the following excerpt:                In our research into chlorophylls of marine dinoflagellates, chlorophyll a was separated rapidly from the hexane extract of Amphidinium carterae in three steps. The first step was silica gel column chromatography, where elution was performed with 0-50% ethyl acetate in n-hexane. The second was high-speed counter-current chromatography using a two-phase solvent system consisting of n-hexane-ethyl acetate-methanol-water (5:5:5:1, v/v), and the third step was preparative reversed-phase high-performance liquid chromatography using a solvent system of acetone-water (89:11, v/v). HPLC analysis showed that the purity of chlorophyll a from the second step was over 83%, and after the third it was over 99%. Thirty milligrams of chlorophyll a was isolated from a crude sample of 250 mg of chlorophylls, and its structure was identified by analyzing its MS, 1H NMR and 13C NMR spectra.Lijuan Long et al., “Development of an efficient method for the preparative isolation and purification of chlorophyll a from a marine dinoflagellate Amphidinium carterae by high-speed counter-current chromatography coupled with reversed-phase high-performance liquid chromatography,” Analytical and Bioanalytical Chemistry, 386(7-8), 2169-74 (December 2006). This article was published after applicant's priority provisional application, and therefore it should not be construed to be prior art to the present application. Even so, the process disclosed in this publication can be distinguished from disclosed embodiments. This article describes a multi-step process that would not be amenable to commercial production of useful quantities of desired materials. For example, the process involves silica chromatography, followed by counter current chromatography, and finally preparatory high pressure liquid chromatography. Preparative HPLC, which is a known method, alone would have been sufficient to obtain small quantities of material. Preparative HPLC is a tedious procedure. Long et al. also teach using silica gel chromatography, but the silica gel chemically modifies chlorophylls. For example, silica gel has been used to oxidize chlorophylls. Thus, the methodology described in the Long et al. publication likely is not suitable for producing commercially useful quantities of desired materials without the possibility of associated chemical modification of desired products. Moreover, the NMR data provided in this publication does not match the authentic sample of chlorophyll a. As a result, a new method for producing useful quantities of intact materials is still desired.        